To study protein metabolism in patients with end-stage renal disease, we measured leucine kinetics in 8 patients. Study was performed twice before and once after (period III)( initiation of maintenance dialysis treatment. Before dialysis, one measurement was done when the patients are acidotic (period I), and the other during sodium bicarbonate supplementation when acidosis was corrected (period II). Sequence of Periods I and II were randomized. Subjects were on identical constant diet during all three periods. Leucine kinetics was measured during primed-constant infusion of [1-13C]leucine, [1-13C]KIC or ( keto-isocaproate and expired breath CO2 enrichment were directly determined. These values were used to calculate leucine appearance rates into the plasma leucine pool and into the total body leucine pool and leucine oxidation rate. The former represents protein degradation rat; protein synthesis rate was indirectly estimated by mass balance equation. The h igher leuc ine oxidation rate without bicarbonate supplementation was not due to higher VCO2 as total CO2 production rate was not different during the three periods. Alternatively, higher proportion of endogenously produced CO2 may be excreted than in the non-acidotic state. Finally, these findings may represent a real enhancement of amino acid oxidation in the presence of metabolic acidosis.